Recent preclinical and clinical studies suggest that lorcaserin, a preferential serotonin 2C receptor (5-HT2CR) agonist that was approved for the treatment of obesity, possesses antiepileptic properties. Here, we tested whether lorcaserin (1, 3, 5.6, 10 mg/kg) is prophylactic against audiogenic seizures (AGSs) in juvenile Fmr1 knockout mice, a mouse model of fragile X syndrome (FXS). MPEP (30 mg/kg), a non-competitive mGluR5 receptor antagonist, was used as a positive control. As lorcaserin likely engages 5-HT2ARs at therapeutic doses, we pretreated one group of mice with the selective 5-HT2AR antagonist/inverse agonist, M100907 (0.03 mg/kg), alone or before administering lorcaserin (5.6 mg/kg), to discern putative contributions of 5-HT2ARs to AGSs. We also assessed lorcaserin's in vitro pharmacology at human (h) and mouse (m) 5-HT2CRs and 5-HT2ARs and its in vivo interactions at m5-HT2CRs and m5-HT2ARs. MPEP significantly decreased AGS prevalence (P = 0.011) and lethality (P = 0.038). Lorcaserin, 3 mg/kg, ate (P = 0.01 and P = 0.03), however, the HTR was much lower than what was elicited by DOI or DOI plus lorcaserin. Lorcaserin, 3 mg/kg, significantly reduced locomotor activity on its own, an effect reversed by SB 242084, and lorcaserin also dose-dependently reduced locomotor activity when administered prior to DOI (Ps less then 0.002). These data suggest that lorcaserin may engage 5-HT2CRs as well as 5-HT2ARs in mice at doses as low as 3 mg/kg. The similar activity at m5-HT2CRs and m5-HT2ARs suggests careful dosing of lorcaserin is necessary to selectively engage 5-HT2CRs in vivo. In conclusion, lorcaserin was ineffective at preventing AGSs in Fmr1 knockout mice. Lorcaserin may not be a suitable pharmacotherapy for seizures in FXS.To compare hip extensor strength and corticomotor excitability (CME) of gluteus maximus (GM) between males and females. A secondary purpose was to determine if CME of GM is predictive of hip extensor strength.
Thirty-two healthy individuals participated (15 males and 17 females). CME of GM was assessed using the input-output curve (IOC) procedure acquired from transcranial magnetic stimulation (average slope). Hip extensor strength was measured by a dynamometer during a maximal voluntary isometric contraction. Independent t-tests were used to compare CME of GM and peak hip extensor torque between males and females. Linear regression analysis was used to determine whether peak hip extensor torque was predicted by CME of GM.
Compared to males, females demonstrate lower peak hip extensor torque (4.42±1.11 vs. 6.15±1.72Nm/kg/m2, p&lt;0.01) and lower CME of GM (1.36±1.07 vs. 2.67±1.30, p&lt;0.01). CME of GM was a significant predictor of peak hip extensor torque for males and females combined (r=0.36, p&lt;0.001).
Our findings support the premise that corticomotor excitability plays a role in the ability of a muscle to generate torque.
Our findings support the premise that corticomotor excitability plays a role in the ability of a muscle to generate torque.International migration from Sub-Saharan African countries to the European Union and the United States has significantly increased over the past decades. Although the vast majority of these immigrants are young and healthy people, a minority can be affected by chronic conditions eventually leading to solid organ transplantation (SOT). Importantly, these candidates can bear geographically restricted fungal and parasitic latent infections that can reactivate after the procedure. An appropriate evaluation before transplantation followed by treatment, whenever necessary, is essential to minimize such risk, as covered in the present review. In short, infection due to helminths (Schistosoma spp. and Strongyloides stercoralis) and intestinal protozoa (Entamoeba histolytica, Giardia lamblia or Cyclospora cayetanensis) can be diagnosed by multiple direct stool examination, serological assays and stool antigen testing. Leishmaniasis can be assessed by means of serology, followed by nucleic acid amplification testing (NAAT) if the former test is positive. Submicroscopic malaria should be ruled out by NAAT. Screening for Histoplasma spp. or Cryptococcus spp. is not routinely indicated. Consultation with an Infectious Diseases specialist is recommended in order to adjust preemptive treatment among Sub-Saharan African SOT candidates and recipients.Monitoring of concrete behavior is an important task to evaluate the safety of concrete structures. This paper proposes a new stretching factor accumulation method based on the stepwise coda wave interference (CWI) to accurately calculate the relative velocity change Δv/v. The Δv/v and residual decorrelation coefficient Kd are used to study the concrete behavior in step loading experiment and short-time fixed loading experiment. The results show that (1) In the loading stage of step loading experiments, both Δv/v and Kd can be used to monitor the load and the microcrack development; (2) In the relaxation stage of step loading experiments, the slow dynamics effect of concrete specimens can be characterized by Δv/v and Kd; (3) In the short-time fixed loading experiments, both Δv/v and Kd increase with the time of fixed loading, and the increasing rate of Δv/v decreases with the increase of concrete strength. This work can be used to promote the development of ultrasonic testing techniques that aid in concrete behavior monitoring.Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. https://www.selleckchem.com/products/Idarubicin.html A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms.